Objective lens arrangement for confocal endomicroscopy

ABSTRACT

An apparatus for imaging an anatomical structure(s) can be provided. For example, a housing arrangement can have a shape of a pill and can be to be delivered to the anatomical structure(s). An imaging arrangement can be configured to generate a microscopic image of the anatomical structure(s), wherein the imaging arrangement can include a variable focus lens, and can be provided in the housing arrangement.

CROSS-REFERENCE TO RELATED APPLICATION(S)

This application relates to and claims priority from U.S. Patent Application Ser. No. 61/759,727 filed Feb. 1, 2013, and U.S. Patent Application Ser. No. 61/799,402 filed Mar. 15, 2013, the entire disclosures of which are incorporated herein by reference.

FIELD OF THE DISCLOSURE

The present disclosure relates to an objective lens for endomicroscopy that can change the focal length while maintaining a relatively high numerical aperture (NA), and in particular to an exemplary compound variable focus objective lens arrangement.

BACKGROUND INFORMATION

The diagnosis of Barrett's esophagus (BE), dysplasia, and intramucosal carcinoma remains an important clinical problem. Video endoscopy, the first-line imaging method used for examination of the esophagus, does not have the contrast or microscopic resolution required to reliably detect the morphologic changes associated with BE progression. As a result, the diagnosis of BE progression currently relies on histopathologic examination of tissues obtained from random endoscopic biopsy. However, this method only allows a very small fraction of the region at risk to be examined and often fails to represent the overall disease status. (See, e.g., Reference 1).

Comprehensive microscopy of the entire distal esophagus offers the potential to provide a more accurate accounting of disease status. Previously, optical frequency domain imaging (OFDI) has been demonstrated to be capable of imaging the entire distal esophagus in vivo through a balloon-centering catheter. (See, e.g., References 2-3). The diagnostic information provided by OFDI can be further used to guide the endoscopic biopsy, which may reduce sampling errors and can enhance diagnostic accuracy. (See, e.g., Reference 4). While OFDI can clearly visualize architectural morphology, cellular features that may be required for the most accurate diagnosis are not well appreciated by OFDI because of its resolution, which is on the order of 10-20 μm.

Confocal laser endomicroscopy (CLE) can visualize cellular and sub-cellular morphology of internal organ tissues in vivo. (See, e.g., References 5-14). Previous studies have shown that CLE can differentiate intestinal metaplasia from normal esophageal tissues (See, e.g., References 6, 15, and 16), and neoplastic changes from intestinal metaplasia (See, e.g., References 6, and 15-17). However, the field size of CLE is typically limited to ˜500 μm×500 μm. As a result, only small fractions of the surface area at risk can be examined during an endoscopy session, and therefore CLE is likely subject to sampling errors that are similar to those found with endoscopic biopsy. (See, e.g., Reference 1). Mosaicing CLE images together has been demonstrated to generate larger confocal images. (See, e.g., References 18 and 19). Even with mosaicing, the frame rate of CLE and the requirement of near contact imaging prohibit interrogation of the entire distal esophagus in realistic procedure times, however.

Spectrally encoded confocal microscopy (SECM) is a confocal microscopy technology that is capable of obtaining images at a rate that is 10 to 100 times faster than that of conventional confocal microscopy systems. (See, e.g., Reference 20). With SECM, a diffraction grating and an objective lens at the distal tip of an optical fiber are used to illuminate different spatial locations on the specimen with distinct spectral bands. Reflected light from the specimen is transferred back through the grating-objective pair and the fiber to the system console. Within the SECM system, one line of the confocal microscopy image is rapidly acquired by measuring the spectral content of the remitted light using a high-speed spectrometer (e.g., a broadband input) or a high-bandwidth photodetector (e.g., a wavelength swept source input). The other dimension of the image is obtained while scanning the grating-objective pair perpendicularly to the spectrally encoded line. In a clinical study of imaging esophageal biopsy samples, SECM has been demonstrated to visualize architectural and cellular features similar to those used for histologic diagnosis. (See, e.g., Reference 21). In an earlier work, the feasibility of imaging large luminal organs was demonstrated (See, e.g., Reference 22) using a bench top setup designed to simulate SECM imaging through a balloon-centering probe. In this paper, the spectrally encoded line was helically scanned across static cylindrical specimens with similar dimensions to the human distal esophagus. This device captured large-area confocal images at a fixed focal distance and needed to conduct multiple helical scans at different focal locations to acquire volumetric data. (See, e.g., Reference 22).

One key challenge for conducting comprehensive esophageal imaging in vivo with SECM is that the focal plane of the objective lens must be consistently kept at a designated imaging depth within the tissue. Because the numerical aperture (NA) is large in SECM (˜0.5), the confocal parameter or depth of focus is small, making the device very sensitive to variations in the distance between the probe and the tissue. Maintaining a constant focal distance is therefore quite difficult in the presence of tissue surface irregularity and motion encountered when imaging living patients. Recently, to solve the above problem, we have implemented adaptive focusing mechanism using piezo-electric transducer (PZT) to the SECM probe that senses the tissue surface and automatically adjusts the focal location of the objective lens while the probe scans tissue. (See, e.g., Reference 23).

While SECM probe equipped with an adaptive focusing mechanism with PZT shows significant potential, its size, stability (e.g., hysteresis) and usage of high voltage may not necessarily be sufficient for SECM imaging probe.

Thus, there may be a need to provide a new mechanism of adaptive focusing, e.g., variable focus objective lens that is capable of creating many lenses with different curvatures that can be changed by controlling the surface of the liquid pressure or volume without any moving parts. This variable focus liquid lens can be applied to confocal endomicroscopy imaging, if variable focus liquid lens has a relatively high NA. However, most of proposed variable focus liquid lens has low NA value such as 0.1-0.2 because it is difficult to fabricate a high NA surface with polymer membrane for variable focus liquid lens. In this patent, we describe a new variable focus liquid lens that can change the focal length while maintaining a relatively high NA.

SUMMARY OF EXEMPLARY EMBODIMENTS

Compound variable focus objective lens is an adaptive focusing method for endomicroscopy imaging, which can change focal length while maintaining high NA. This lens is composed of an aspheric singlet that has been assembled with a variable focus liquid lens. Most of the optical power is provided by the aspheric singlet, and the variable focus liquid lens changes the optical power slightly to change the focal length.

The exemplary compound variable focus objective lens can have certain advantages as follows. First, the exemplary lens can be miniaturized and/or reduce easily for endomicroscopy because the apparatus does not need any moving parts such as a PZT, voice coil motor, deformable mirror and shape memory alloy, etc. Second, the exemplary focus can be changed by water pressure, which is biocompatible material for endoscopy field and also already has been used in various endoscopy diagnosis and surgery.

According to an exemplary embodiment of the present disclosure, the compound variable focus objective lens can be based on SECM endoscopic probe specifications. Further, exemplary variable focus objective lens parameters can be designed based on custom objective lens parameters by ZEMAX. It is possible to, according to an exemplary embodiment of the present disclosure, to utilize an aspheric singlet (molded glass aspheric singlet; material=L-LAH84; focal length=about 1.6 mm; NA=about 0.44) and an internally fabricated variable focus liquid lens (liquid=water; liquid refractive index=about 1.33; liquid chamber thickness=about 0.5 mm; Polydimethylsiloxane (PDMS) membrane thickness: about 130 μm). This exemplary combination of elements can provide a NA of about 0.40-0.46, while the focal length can be changed over a 617 μm range, approximately.

The compound variable focus objective lens according to an exemplary embodiment of the present disclosure can be utilized in and for all the fields where a relatively high NA variable focus lens is preferred or needed. For example, the compound variable focus objective lens can be widely used in the field of microscopic imaging, as well as in various other fields.

To that end, an exemplary apparatus according to an exemplary embodiment of the present disclosure can be provided for imaging an anatomical structure(s). Such exemplary apparatus can include a housing arrangement that can have a shape of a pill, and can be delivered to the anatomical structure(s). An imaging arrangement can be configured to generate a microscopic image of the anatomical structure(s). The imaging arrangement can include a variable focus lens, and can be provided in the housing arrangement. The imaging arrangement can operate based on reflectance confocal microscopy, SECM, OFDI, SD-OCT, FFOCM, first, 2nd harmonic microscopy, fluorescence microscopy or RAMAN.

In certain exemplary embodiments of the present disclosure, a hydraulic arrangement can be used to control a focus of the variable focus lens. In some exemplary embodiments of the present disclosure, the housing arrangement can be configured to be delivered to be the anatomical structure(s). The length of the pill can be less than 35 mm, and a width of the pill can be less than 15 mm, and the imaging arrangement can be a tether that can be connected to the pill. In certain exemplary embodiments of the present disclosure, the variable focus lens can be a fluid-filled lens.

In yet another exemplary embodiment of the present disclosure, an exemplary apparatus can be provided for imaging an anatomical structure(s), which can include an imaging arrangement that can be configured to generate a microscopic image of the anatomical structure(s). The imaging arrangement can include a variable focus fluid-filled lens.

According to still a further exemplary embodiment of the present disclosure, an exemplary apparatus can be provided for imaging an anatomical structure(s), which can include an imaging arrangement which can be configured generate a microscopic image of the anatomical structure(s). The imaging arrangement can include a microscope objective lens arrangement that can provide a variable focus. The lens arrangement can include a variable focus first lens and second lens. The first lens and/or the second lens can have an aspherical surface, and the first and second lenses can be attached to one another. The second lens can be a single element lens. In certain exemplary embodiments of the present disclosure, a numerical aperture of the microscope objective lens arrangement can be higher than 0.5.

In a yet a further embodiment of the present disclosure, an exemplary apparatus can be provided for imaging an anatomical structure(s), which can include an imaging arrangement which can be configured to generate a microscopic image of the anatomical structure(s). The imaging arrangement can include a microscope objective lens arrangement providing a variable focus. The lens arrangement can include a variable focus first lens and a second lens which can be attached to one another.

These and other objects, features and advantages of the exemplary embodiments of the present disclosure will become apparent upon reading the following detailed description of the exemplary embodiments of the present disclosure, when taken in conjunction with the appended claims.

BRIEF DESCRIPTION OF THE DRAWINGS

Further objects, features and advantages of the present disclosure will become apparent from the following detailed description taken in conjunction with the accompanying figures showing illustrative embodiments of the present disclosure, in which:

FIG. 1 is a diagram of an exemplary compound variable focus objective lens, according to an exemplary embodiment of the present disclosure;

FIG. 2A is a cross-sectional view of the compound variable focus objective lens with curvature deformation according to an exemplary embodiment of the present disclosure without a liquid pressure;

FIG. 2B is a cross-sectional view of the compound variable focus objective lens with curvature deformation according to the exemplary embodiment of the present disclosure with a liquid pressure;

FIG. 3 is an exemplary SECM scan image with the exemplary compound variable focus objective lens according to an exemplary embodiment of the present disclosure;

FIG. 4 is a set of exemplary images of a lens paper phantom obtained at different imaging depth levels (surface curvature or liquid volume) generated using an exemplary SECM system with the exemplary compound variable focus objective lens according to an exemplary embodiment of the present disclosure;

FIG. 5 is a cross-sectional view of an exemplary SECM endoscopic probe with the exemplary compound variable focus objective lens according to an exemplary embodiment of the present disclosure which uses a hydraulic pressure;

FIG. 6 is a cross-sectional view of the exemplary SECM endoscopic probe with the exemplary compound variable focus objective lens according to another exemplary embodiment of the present disclosure which uses an exemplary PZT actuator;

FIG. 7 is a cross-sectional view of an exemplary SECM pill probe with the exemplary compound variable focus objective lens according to an exemplary embodiment of the present disclosure which uses a hydraulic pressure; and

FIG. 8 is a cross-sectional view of the exemplary SECM pill probe with the exemplary compound variable focus objective lens according to another exemplary embodiment of the present disclosure which uses PZT actuator.

Throughout the figures, the same reference numerals and characters, unless otherwise stated, are used to denote like features, elements, components or portions of the illustrated embodiments. Moreover, while the subject disclosure will now be described in detail with reference to the figures, it is done so in connection with the illustrative embodiments. It is intended that changes and modifications can be made to the described embodiments without departing from the true scope and spirit of the subject disclosure as defined by the appended claims.

DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS

Hereinafter, structures, configurations and operating principles of a variable focus objective lens according to various exemplary embodiments of the present disclosure will be described with reference to the attached drawings.

FIG. 1 a diagram of an exemplary compound variable focus objective lens 102, according to an exemplary embodiment of the present disclosure. This exemplary objective lens can include an aspheric singlet 105 that can be assembled with a variable focus liquid lens 102 and the aspheric singlet 105. For example, the variable focus liquid lens 102 can be combined by a lens holder 103 and a spacer 104. Most of the optical power can be provided by the aspheric singlet 105, and the variable focus liquid lens 102 can change the optical power slightly to modify the focal length (as shown in FIG. 1). One or more surfaces 101 of the variable focus liquid lens 105 can be made from and/or with a thin polymer membrane. The exemplary curvature of the membrane surface 101 of the variable focus liquid lens 105 can be controlled quantitatively by, e.g., a pressure controller 109 and a pressure sensor 110 via a water delivery path 108 or the like. Thus, e.g., the focal plane 6 can be changed by a curvature of the membrane surface 101.

FIGS. 2A and 2B illustrate cross-sectional views of the exemplary variable focus liquid lens with a curvature deformation according to exemplary embodiments of the present disclosure with and/or without liquid pressure being applied. For example, as shown in FIGS. 2A and 2B, the compound variable focus objective lens according to the exemplary embodiment of the present disclosure can include a custom objective lens 215 (e.g., a molded glass aspheric singlet; material=L-LAH84; focal length=1.6 mm; NA=0.44) for a confocal endomicroscopy with a metal mold 211, PDMS objective lens holder 212 to combine the objective lens 215 with variable focus liquid lens (e.g., the PDMS objective lens holder 212 and the PDMS membrane 213, 313). The liquid pressure or volume of a liquid chamber 252 can be changed by the pressure controller 109 via a liquid path 214, For example, there can be two or more liquid paths for the liquid input and output to remove air bubbles. According to the pressure of the liquid chamber 252, the curvature of the PDMS membrane 213, 313 can be thus changed, and therefor the focal length can be modified.

FIG. 3 shows an SECM scan image of a 1951 USAF resolution chart generated by an exemplary system with the exemplary compound variable focus objective lens according to an exemplary embodiment of the present disclosure. For example, to smallest bars (Group 7, Element 6), can be separated by an exemplary distance of, e.g., about 2.2 μm.

FIG. 4 illustrates a set of exemplary images of a lens paper phantom obtained at different imaging depth levels (e.g., the surface curvature or liquid volume) by an exemplary system with the exemplary compound variable focus objective lens according to an exemplary embodiment of the present disclosure. For example, a stack of en face confocal images can be acquired while changing the water pressure. Exemplary morphologic changes in the images are illustrated between different images, e.g., confirming the variable focusing capability of the exemplary objective lens described herein.

An exemplary cross-sectional illustration of an exemplary SECM endoscopic probe with the exemplary compound variable focus lens that uses a hydraulic pressure according to an exemplary embodiment of the present disclosure is shown in FIG. 5. For example, as illustrated in FIG. 5, the exemplary SECM endoscopic probe can include a double-clad fiber (DCF) 1211 which can transceive the imaging light or other electro-magnetic radiation. The fiber 1211 can be contained within or provided with a driveshaft 1216 that can rotate. By rotating and/or translating the driveshaft at its proximal end, it is possible to facilitate an exemplary helical imaging. During imaging, a control signal, derived from the reflection from an imaging tube surface 1232 and an esophagus tissue 330 can be used to generate an input to the compound variable focus objective lens 1242 through the liquid delivery tube 1234 to adaptively change the focal location. The driveshaft 1212 and the DCF 1211 can be attached to an exemplary SECM probe housing, 1217, which can include collimation optics 220, a grating 130, liquid delivery tube 1234 and a compound variable focus objective lens 1242. The distal end of the probe exemplary can be terminated by a guide wire provision 1231.

An exemplary cross-sectional illustration of the exemplary SECM endoscopic probe with the exemplary compound variable focus lens that uses an exemplary PZT actuator according to another exemplary embodiment of the present disclosure is illustrated in FIG. 6. Such exemplary SECM endoscopic probe shown in FIG. 6 can include a double-clad fiber (DCF) 1211 which can transceive the imaging light or other electromagnetic radiation. Similarly to the exemplary embodiment shown in FIG. 5, the fiber 1211 can be provided within the driveshaft 1216 that can rotate. Again, by botating and translating the driveshaft 1216 at its proximal end, it is possible to facilitate an exemplary helical imaging. Further, according to this exemplary embodiment, during imaging, a control signal, derived from the reflection from the imaging tube surface 1232 and the esophagus tissue 330, can be used to generate an input signal to a PZT 750 for changing the pressure of a chamber 620, that can be connected to the exemplary compound variable focus objective lens 1242 to adaptively change the focal location. Further, the PZT 750 can be connected to the proximal end using electrical wire 1234. The driveshaft 1212 and the DCF 1211 can be attached to the SECM probe housing 1217, which can include the collimation optics 220, the grating 130, the liquid delivery tube 1234 and the exemplary compound variable focus objective lens 1242. As with the exemplary probe of FIG. 6, the distal end of the exemplary probe shown in FIG. 6 can be terminated by the guide wire provision 1231.

FIG. 7 shows an exemplary illustration of an exemplary SECM pill arrangement with the exemplary compound variable focus objective lens according to an exemplary embodiment of the present disclosure which can use the hydraulic pressure. The exemplary SECM pill arrangement shown in FIG. 7 can include a double-clad fiber (DCF) 1311, which can transceive the imaging light or other electromagnetic radiation. The exemplary fiber 131 can be contained within a driveshaft 1316 that can rotate. As with the exemplary embodiments shown in FIGS. 5 and 6, the rotation and/or the translation of the driveshaft 1316 at its proximal end can facilitate an exemplary helical imaging. During such exemplary imaging, a control signal, derived from the reflection from a pill surface 1317 and an esophagus tissue 430, can be used to generate an input to the exemplary compound variable focus objective lens 1342 through or via a liquid delivery tube 1314 to, e.g., adaptively change the focal location. The driveshaft 1316 and the DCF 1311 can be attached or otherwise connected to the SECM pill arrangement 1317, which can include the collimation lens 230, the grating 530, the liquid delivery tube 1314 and the compound variable focus objective lens 1342.

FIG. 8 shows an exemplary illustration of the exemplary SECM pill arrangement with the exemplary compound variable focus objective lens according to an exemplary embodiment of the present disclosure which can use an exemplary PZT actuator. The exemplary SECM pill arrangement of FIG. 8 can include substially the same components and devices described herein above with respect to the exemplary pill arrangement shown in FIG. 7. Further, in this exemplary embodiment, during imaging, the control signal, derived from the reflection from the pill surface 1317 and the esophagus tissue 430, can be used to generate an input signal to a PZT actuator 850 for changing the pressure of a chamber 720 which can be connected to the exemplary compound variable focus objective lens 1342 to adaptively change the focal location. Further, the PZT actuator 850 can be connected to the proximal end using electrical wire 1314, so as facilitate the compound variable focus objective lens 1342 to adaptively change the focal location.

Table 1 depicts the exemplary design specifications for the exemplary compound variable focus objective lens. The exemplary compound variable focus objective lens can have a NA range of 0.4-0.46 and adaptive focusing range of about 617 μm within 0.07 RMS wavefront error.

TABLE 1 Specification Value Lens diameter 5 mm RMS wavefront error <0.07 Adaptive focusing range 617 μm Focal length 2.13 mm Optical liquid Water PDMS membrane thickness 130 μm Liquid chamber thickness 1.0 mm Numerical aperture (NA) 0.4-0.46

The foregoing merely illustrates the principles of the disclosure. Various modifications and alterations to the described embodiments will be apparent to those skilled in the art in view of the teachings herein. Indeed, the arrangements, systems and methods according to the exemplary embodiments of the present disclosure can be used with and/or implement any OCT system, OFDI system, SD-OCT system or other imaging systems, and for example with those described in International Patent Application PCT/US2004/029148, filed Sep. 8, 2004 which published as International Patent Publication No. WO 2005/047813 on May 26, 2005, U.S. patent application Ser. No. 11/266,779, filed Nov. 2, 2005 which published as U.S. Patent Publication No. 2006/0093276 on May 4, 2006, and U.S. patent application Ser. No. 10/501,276, filed Jul. 9, 2004 which published as U.S. Patent Publication No. 2005/0018201 on Jan. 27, 2005, and U.S. Patent Publication No. 2002/0122246, published on May 9, 2002, the disclosures of which are incorporated by reference herein in their entireties. It will thus be appreciated that those skilled in the art will be able to devise numerous systems, arrangements, and procedures which, although not explicitly shown or described herein, embody the principles of the disclosure and can be thus within the spirit and scope of the disclosure. In addition, all publications and references referred to above can be incorporated herein by reference in their entireties. It should be understood that the exemplary procedures described herein can be stored on any computer accessible medium, including a hard drive, RAM, ROM, removable disks, CD-ROM, memory sticks, etc., and executed by a processing arrangement and/or computing arrangement which can be and/or include a hardware processors, microprocessor, mini, macro, mainframe, etc., including a plurality and/or combination thereof. In addition, certain terms used in the present disclosure, including the specification, drawings and claims thereof, can be used synonymously in certain instances, including, but not limited to, e.g., data and information. It should be understood that, while these words, and/or other words that can be synonymous to one another, can be used synonymously herein, that there can be instances when such words can be intended to not be used synonymously. Further, to the extent that the prior art knowledge has not been explicitly incorporated by reference herein above, it can be explicitly being incorporated herein in its entirety. All publications referenced above can be incorporated herein by reference in their entireties.

EXEMPLARY REFERENCES

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Numbered what is claimed is:
 1. An apparatus for imaging at least one anatomical structure, comprising: a housing comprising a curved-edge pill and configured to be delivered to the at least one anatomical structure; an imaging arrangement disposed within the housing and comprising a grating and a variable focus lens which is configured to generate a microscopic image of the at least one anatomical structure, wherein the variable focus lens comprises a membrane; and a pressure control actuator connected to the variable focus lens via a liquid path, and configured to automatically control a pressure or a volume of the variable focus lens, wherein the imaging arrangement and the pressure control actuator are provided in the housing arrangement, wherein the pressure control actuator receives a control signal based on reflections obtained from the housing and based on reflections obtained from the at least one anatomical structure, and automatically controls a focus of the variable focus lens based on receiving the control signal.
 2. The apparatus according to claim 1, wherein the imaging arrangement receives information provided by at least one of the following modalities: reflectance confocal microscopy, spectrally encoded confocal microscopy (SECM), optical frequency domain interferometry (OFDI), spectral domain optical coherence tomography (SD-OCT), fluorescence microscopy or Raman spectroscopy, and generates the microscopic image based on the information.
 3. The apparatus according to claim 1, wherein the pressure control actuator further comprises a piezo-electric transducer to automatically control the focus of the variable focus lens.
 4. The apparatus according to claim 1, wherein the housing arrangement is configured to be delivered to an anatomical structure.
 5. The apparatus according to claim 1, wherein a length of the housing arrangement is less than 35 mm, and a width of the housing arrangement is less than 15 mm.
 6. The apparatus according to claim 1, wherein the imaging arrangement includes a tether that is connected to or via the housing arrangement.
 7. The apparatus according to claim 1, wherein the variable focus lens is a fluid-filled lens.
 8. An apparatus for imaging at least one anatomical structure, comprising: an imaging arrangement comprising a grating and a variable focus fluid-filled lens which is configured to generate data to produce a microscopic image of the at least one anatomical structure, wherein the variable focus fluid-filled lens comprises a membrane, and wherein a change of a pressure or a volume of a fluid within the variable focus fluid-filled lens changes a radius of curvature of at least one surface of the variable focus fluid-filled lens; and a pressure control actuator connected to the variable focus fluid-filled lens via a liquid path, and configured to automatically control the pressure or the volume of the variable focus fluid-filled lens, wherein the pressure control actuator receives a control signal based on reflections from the at least one anatomical structure and based on reflections obtained from the housing, and automatically controls a focus of the variable focus lens based on the control signal.
 9. The apparatus according to claim 8, wherein the imaging arrangement receives information provided by at least one of the following modalities: reflectance confocal microscopy, spectrally encoded confocal microscopy (SECM), optical frequency domain interferometry (OFDI), spectral domain optical coherence tomography (SD-OCT), fluorescence microscopy or Raman spectroscopy, and generates the microscopic image based on the information.
 10. The apparatus according to claim 8, wherein the pressure control actuator further comprises a piezo-electric transducer to automatically control the focus of the variable focus fluid-filled lens.
 11. An apparatus for imaging at least one anatomical structure, comprising: an imaging arrangement comprising a grating and a microscope objective lens which is configured to generate a microscopic image of the at least one anatomical structure, wherein the microscope objective lens provides a variable focus, and wherein the microscope objective lens comprises at least one variable focus first lens comprising a membrane and at least one fixed focus second lens, wherein the fixed focus second lens has a curved aspherical surface; and a pressure control actuator connected to the variable focus first lens, wherein the pressure control actuator automatically controls the variable focus first lens based on reflections obtained from the housing and based on reflections obtained from the at least one anatomical structure.
 12. The apparatus according to claim 11, wherein the first and second lenses are attached to one another.
 13. The apparatus according to claim 11, wherein the at least one second lens is a single element lens.
 14. The apparatus according to claim 11, wherein a numerical aperture of the microscope objective lens arrangement is higher than 0.5.
 15. The apparatus according to claim 11, wherein the imaging arrangement receives information provided by at least one of the following modalities: reflectance confocal microscopy, spectrally encoded confocal microscopy (SECM), optical frequency domain interferometry (OFDI), spectral domain optical coherence tomography (SD-OCT), fluorescence microscopy or Raman spectroscopy, and generates the microscopic image based on the information.
 16. The apparatus according to claim 11, wherein the pressure control actuator further comprises a piezo-electric transducer to automatically control the focus of the variable focus first lens.
 17. An apparatus for imaging at least one anatomical structure, comprising: an imaging arrangement comprising a grating and a microscope objective lens which is configured to generate a microscopic image of the at least one anatomical structure, wherein the microscope objective lens provides a variable focus, and wherein the lens arrangement comprises at least one variable focus first lens comprising a membrane and at least one fixed focus second lens which are directly attached to one another, wherein the fixed focus second lens has a curved aspherical surface; and a pressure control actuator connected to the variable focus first lens, wherein the pressure control actuator receives a control signal based on reflections obtained from the housing and based on reflections obtained from the at least one anatomical structure, and automatically controls a focus of the variable focus first lens based on the control signal.
 18. The apparatus according to claim 17, wherein the imaging arrangement receives information provided by at least one of the following modalities: reflectance confocal microscopy, spectrally encoded confocal microscopy (SECM), optical frequency domain interferometry (OFDI), spectral domain optical coherence tomography (SD-OCT), fluorescence microscopy or Raman spectroscopy, and generates the microscopic image based on the information.
 19. The apparatus according to claim 17, wherein the pressure control actuator further comprises a piezo-electric transducer to automatically control the focus of the microscope objective first lens. 